Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5

書誌事項

公開日
2004-04-01
DOI
  • 10.1101/gad.1180104
公開者
Cold Spring Harbor Laboratory

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説明

<jats:p>Mammalian oxygen homeostasis is dependent on the HIF family of transcription factors. The CSN subunit, CSN5, binds both the CODD of HIF-1α and the pVHL tumor suppressor. High CSN5 expression generates a pVHL-independent form of CSN5 that stabilizes HIF-1α aerobically by inhibiting HIF-1α prolyl-564 hydroxylation. Aerobic CSN5 association with HIF-1α occurs independently of the CSN holocomplex, leading to HIF-1α stabilization independent of Cullin 2 deneddylation. CSN5 weakly associates with HIF-1α under hypoxia, but is required for optimal hypoxia-mediated HIF-1α stabilization. These results indicate that CSN5 regulates aerobic as well as hypoxic HIF-1α stability by different mechanisms during oncogenesis.</jats:p>

収録刊行物

  • Genes & Development

    Genes & Development 18 (7), 739-744, 2004-04-01

    Cold Spring Harbor Laboratory

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